Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes
Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2017-07, Vol.66 (7), p.1939-1949 |
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| creator | Lytvyn, Yuliya Har, Ronnie Locke, Amy Lai, Vesta Fong, Derek Advani, Andrew Perkins, Bruce A Cherney, David Z I |
| description | Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (
= 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (
= 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (R
), and glomerular hydrostatic pressure (P
). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg,
= 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in R
P
, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal R
responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D. |
| doi_str_mv | 10.2337/db17-0168 |
| format | Article |
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= 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (
= 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (R
), and glomerular hydrostatic pressure (P
). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg,
= 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in R
P
, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal R
responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db17-0168</identifier><identifier>PMID: 28408434</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Adult ; Aldosterone ; Angiotensin ; Angiotensin II ; Angiotensin II - pharmacology ; Blood Pressure ; Case-Control Studies ; Clinical trials ; Cytokines ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - drug therapy ; Diabetes Mellitus, Type 1 - metabolism ; Diabetes Mellitus, Type 1 - physiopathology ; Febuxostat - therapeutic use ; Female ; Glomerular filtration rate ; Glomerular Filtration Rate - drug effects ; Glomerular Filtration Rate - physiology ; Gout Suppressants - therapeutic use ; Humans ; Hyperglycemia ; Hyperglycemia - metabolism ; Hyperglycemia - physiopathology ; Hypertension ; Inflammation ; Interleukin 18 ; Interleukin-18 - metabolism ; Inulin ; Kidneys ; Linear Models ; Male ; Mathematical models ; Nitric oxide ; Nitric Oxide - urine ; Nitroglycerin ; Nitroglycerin - pharmacology ; Renal function ; Renal Plasma Flow, Effective - drug effects ; Renal Plasma Flow, Effective - physiology ; Renin ; Renin-Angiotensin System - drug effects ; Renin-Angiotensin System - physiology ; Sensory neurons ; Uric acid ; Uric Acid - blood ; Vascular Stiffness ; Vasoconstrictor Agents - pharmacology ; Vasodilation - drug effects ; Vasodilation - physiology ; Vasodilator Agents - pharmacology ; Young Adult</subject><ispartof>Diabetes (New York, N.Y.), 2017-07, Vol.66 (7), p.1939-1949</ispartof><rights>2017 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association Jul 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c348t-e1658b66f8a2eefa07ffb733d2ec7011e03b75922f2a5aa8d49b3d2ae35562be3</citedby><cites>FETCH-LOGICAL-c348t-e1658b66f8a2eefa07ffb733d2ec7011e03b75922f2a5aa8d49b3d2ae35562be3</cites><orcidid>0000-0002-5885-0046 ; 0000-0003-4164-0429</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28408434$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lytvyn, Yuliya</creatorcontrib><creatorcontrib>Har, Ronnie</creatorcontrib><creatorcontrib>Locke, Amy</creatorcontrib><creatorcontrib>Lai, Vesta</creatorcontrib><creatorcontrib>Fong, Derek</creatorcontrib><creatorcontrib>Advani, Andrew</creatorcontrib><creatorcontrib>Perkins, Bruce A</creatorcontrib><creatorcontrib>Cherney, David Z I</creatorcontrib><title>Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (
= 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (
= 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (R
), and glomerular hydrostatic pressure (P
). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg,
= 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in R
P
, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal R
responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.</description><subject>Adult</subject><subject>Aldosterone</subject><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Angiotensin II - pharmacology</subject><subject>Blood Pressure</subject><subject>Case-Control Studies</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 1 - drug therapy</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Diabetes Mellitus, Type 1 - physiopathology</subject><subject>Febuxostat - therapeutic use</subject><subject>Female</subject><subject>Glomerular filtration rate</subject><subject>Glomerular Filtration Rate - drug effects</subject><subject>Glomerular Filtration Rate - physiology</subject><subject>Gout Suppressants - therapeutic use</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hyperglycemia - metabolism</subject><subject>Hyperglycemia - physiopathology</subject><subject>Hypertension</subject><subject>Inflammation</subject><subject>Interleukin 18</subject><subject>Interleukin-18 - metabolism</subject><subject>Inulin</subject><subject>Kidneys</subject><subject>Linear Models</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - urine</subject><subject>Nitroglycerin</subject><subject>Nitroglycerin - pharmacology</subject><subject>Renal function</subject><subject>Renal Plasma Flow, Effective - drug effects</subject><subject>Renal Plasma Flow, Effective - physiology</subject><subject>Renin</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Renin-Angiotensin System - physiology</subject><subject>Sensory neurons</subject><subject>Uric acid</subject><subject>Uric Acid - blood</subject><subject>Vascular Stiffness</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilation - physiology</subject><subject>Vasodilator Agents - pharmacology</subject><subject>Young Adult</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtOwzAQRS0EoqWw4AeQJVYsAn4kcbKsSnlIFSDUArvIdsbgKi_sRKh_j6sWNItZ3KOrmYPQOSXXjHNxUyoqIkLT7ACNac7ziDPxcYjGhFAWUZGLETrxfk0IScMcoxHLYpLFPB6j-hUaWWHZlPhNej1U0uG5MaB7j1uDV85qPNW2xIv2B5xtPrFt8FPr6nYIEdQhfpG9hSbw77b_wqtGt3VXWS17KPFy0wGm-NZKBT34U3RkZOXhbL8naHU3X84eosXz_eNsuog0j7M-ApommUpTk0kGYCQRxijBeclAC0IpEK5EkjNmmEykzMo4VyGUwJMkZQr4BF3uejvXfg_g-2Id7g2P-iL4oYzSlNBAXe0o7VrvHZiic7aWblNQUmzFFluxxVZsYC_2jYOqofwn_0zyX0vDcxo</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Lytvyn, Yuliya</creator><creator>Har, Ronnie</creator><creator>Locke, Amy</creator><creator>Lai, Vesta</creator><creator>Fong, Derek</creator><creator>Advani, Andrew</creator><creator>Perkins, Bruce A</creator><creator>Cherney, David Z I</creator><general>American Diabetes Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><orcidid>https://orcid.org/0000-0002-5885-0046</orcidid><orcidid>https://orcid.org/0000-0003-4164-0429</orcidid></search><sort><creationdate>201707</creationdate><title>Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes</title><author>Lytvyn, Yuliya ; Har, Ronnie ; Locke, Amy ; Lai, Vesta ; Fong, Derek ; Advani, Andrew ; Perkins, Bruce A ; Cherney, David Z I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-e1658b66f8a2eefa07ffb733d2ec7011e03b75922f2a5aa8d49b3d2ae35562be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aldosterone</topic><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Angiotensin II - pharmacology</topic><topic>Blood Pressure</topic><topic>Case-Control Studies</topic><topic>Clinical trials</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 1 - blood</topic><topic>Diabetes Mellitus, Type 1 - drug therapy</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Diabetes Mellitus, Type 1 - physiopathology</topic><topic>Febuxostat - therapeutic use</topic><topic>Female</topic><topic>Glomerular filtration rate</topic><topic>Glomerular Filtration Rate - drug effects</topic><topic>Glomerular Filtration Rate - physiology</topic><topic>Gout Suppressants - therapeutic use</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Hyperglycemia - metabolism</topic><topic>Hyperglycemia - physiopathology</topic><topic>Hypertension</topic><topic>Inflammation</topic><topic>Interleukin 18</topic><topic>Interleukin-18 - metabolism</topic><topic>Inulin</topic><topic>Kidneys</topic><topic>Linear Models</topic><topic>Male</topic><topic>Mathematical models</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - urine</topic><topic>Nitroglycerin</topic><topic>Nitroglycerin - pharmacology</topic><topic>Renal function</topic><topic>Renal Plasma Flow, Effective - drug effects</topic><topic>Renal Plasma Flow, Effective - physiology</topic><topic>Renin</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Renin-Angiotensin System - physiology</topic><topic>Sensory neurons</topic><topic>Uric acid</topic><topic>Uric Acid - blood</topic><topic>Vascular Stiffness</topic><topic>Vasoconstrictor Agents - pharmacology</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilation - physiology</topic><topic>Vasodilator Agents - pharmacology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lytvyn, Yuliya</creatorcontrib><creatorcontrib>Har, Ronnie</creatorcontrib><creatorcontrib>Locke, Amy</creatorcontrib><creatorcontrib>Lai, Vesta</creatorcontrib><creatorcontrib>Fong, Derek</creatorcontrib><creatorcontrib>Advani, Andrew</creatorcontrib><creatorcontrib>Perkins, Bruce A</creatorcontrib><creatorcontrib>Cherney, David Z I</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lytvyn, Yuliya</au><au>Har, Ronnie</au><au>Locke, Amy</au><au>Lai, Vesta</au><au>Fong, Derek</au><au>Advani, Andrew</au><au>Perkins, Bruce A</au><au>Cherney, David Z I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2017-07</date><risdate>2017</risdate><volume>66</volume><issue>7</issue><spage>1939</spage><epage>1949</epage><pages>1939-1949</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (
= 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (
= 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (R
), and glomerular hydrostatic pressure (P
). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg,
= 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in R
P
, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal R
responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>28408434</pmid><doi>10.2337/db17-0168</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-5885-0046</orcidid><orcidid>https://orcid.org/0000-0003-4164-0429</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 0012-1797 1939-327X |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult Aldosterone Angiotensin Angiotensin II Angiotensin II - pharmacology Blood Pressure Case-Control Studies Clinical trials Cytokines Diabetes Diabetes mellitus Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - drug therapy Diabetes Mellitus, Type 1 - metabolism Diabetes Mellitus, Type 1 - physiopathology Febuxostat - therapeutic use Female Glomerular filtration rate Glomerular Filtration Rate - drug effects Glomerular Filtration Rate - physiology Gout Suppressants - therapeutic use Humans Hyperglycemia Hyperglycemia - metabolism Hyperglycemia - physiopathology Hypertension Inflammation Interleukin 18 Interleukin-18 - metabolism Inulin Kidneys Linear Models Male Mathematical models Nitric oxide Nitric Oxide - urine Nitroglycerin Nitroglycerin - pharmacology Renal function Renal Plasma Flow, Effective - drug effects Renal Plasma Flow, Effective - physiology Renin Renin-Angiotensin System - drug effects Renin-Angiotensin System - physiology Sensory neurons Uric acid Uric Acid - blood Vascular Stiffness Vasoconstrictor Agents - pharmacology Vasodilation - drug effects Vasodilation - physiology Vasodilator Agents - pharmacology Young Adult |
| title | Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes |
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